ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1030T>C (p.Phe344Leu) (rs587781601)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129675 SCV000184474 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-12 criteria provided, single submitter clinical testing The p.F358L variant (also known as c.1072T>C), located in coding exon 12 of the MUTYH gene, results from a T to C substitution at nucleotide position 1072. The phenylalanine at codon 358 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 140000alleles tested) in our clinical cohort.This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000226144 SCV000285914 uncertain significance MYH-associated polyposis 2019-09-10 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 358 of the MUTYH protein (p.Phe358Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs587781601, ExAC 0.03%). This variant has not been reported in the literature in individuals with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 141246). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000226144 SCV000487358 uncertain significance MYH-associated polyposis 2016-05-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129675 SCV000685537 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-09 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 358 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/248812 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759879 SCV000889519 uncertain significance not provided 2018-03-22 criteria provided, single submitter clinical testing

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